Differences among epitopes recognized by neutralizing antibodies induced by SARS-CoV-2 infection or COVID-19 vaccination

SARS-CoV-2 has gradually acquired amino acid substitutions in its S protein that reduce the potency of neutralizing antibodies, leading to decreased vaccine efficacy. Here, we attempted to obtain mutant viruses by passaging SARS-CoV-2 in the presence of plasma samples from convalescent patients or vaccinees to determine which amino acid substitutions affect the antigenicity of SARS-CoV-2. Several amino acid substitutions in the S2 region, as well as the N-terminal domain (NTD) and receptor-binding domain (RBD), affected the neutralization potency of plasma samples collected from vaccinees, indicating that amino acid substitutions in the S2 region as well as those in the NTD and RBD affect neutralization by vaccine-induced antibodies. Furthermore, the neutralizing potency of vaccinee plasma samples against mutant viruses we obtained or circulating viruses differed among individuals. These findings suggest that genetic backgrounds of vaccinees influence the recognition of neutralizing epitopes

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

Theoretical analysis of mixed irradiation (3)

As the model we proposed last year was contradictory to experimental data, we revised again the models for mixed irradiation by Zaider and Rossi and by Suzuki, substituting a \u27reciprocal-time\u27 pattern of repair function for a first-order one in reduction and interaction factors of the models, although we used a second order repair function last year. The reduction factor, which reduces the contribution of the square of a dose to cell killing in the models, and the interaction factor, which also reduces the contribution of the interaction of two or more doses of different types of radiation, were formulated by using the \u27reciprocal-time\u27 pattern of repair function. These newly modified models for mixed irradiation could express or predict cell survival more accurately than the older ones, especially when irradiation is prolonged at low dose rates. We present survival curves of cells calculated from the newly and the older models of assumptive simultaneous mixed irradiation with two or three types of radiation

A linear-quadratic model for mixed irradiation with multiple types of radiation observed in the space

We revised the model of Suzuki for mixed irradiation with multiple types of radiation, substituting a \u27reciprocal-time\u27 pattern of repair function for a first-order one in reduction and interaction factors of the model. The reduction factor, which reduces the contribution of the square of a dose to cell killing in the model, and the interaction factor, which also reduces the contribution of the interaction of two or more doses of different types of radiation, were formulated by using the \u27reciprocal-time\u27 pattern of repair function. The newly modified models for mixed irradiation could express or predict cell survival more accurately than the older ones, especially when irradiation is prolonged at low dose rates. We present survival curves of cells calculated from the new and the old models of assumptive simultaneous mixed irradiation with two or three types of radiation.The 2nd International Workshop on Space Radiation Researc